L. Thorlacius

Protocol for the development of a core domain set for hidradenitis suppurativa trial outcomes

Introduction Randomised controlled trials (RCTs) should have well-defined primary and secondary outcomes to answer questions generated by the main hypotheses. However, for the chronic, inflammatory skin disease hidradenitis suppurativa (HS), the reported outcome measures are numerous and diverse. A recent systematic review found a total of 30 outcome measure instruments in 12 RCTs. This use of a broad range of outcome measures can increase difficulties in interpretation and comparison of results and may potentially obstruct appropriate evidence synthesis by causing reporting bias. One strategy for dealing with these problems is to develop a core outcome set (COS). A COS is a list of outcomes that are meant as mandatory and should be measured and reported in all clinical trials. The aim of this study is to develop a COS for the management of HS. Method and analysis An international steering group of researchers, clinicians and a patient research partner will guide the COS development. 6 stakeholder groups are involved: patients, dermatologists, surgeons, nurses, industry representatives and drug regulatory authorities. A 1:1 ratio of patients:healthcare professionals is aimed for. The initial list of candidate items will be obtained by combining three data sets: (1) a systematic review of the literature, (2) US and Danish qualitative interview studies involving patients with HS and (3) an online healthcare professional (HCP) item generation survey. To reach consensus on the COS, 4 anonymous online Delphi rounds are then planned together with 2 face-to-face consensus meetings (1 in Europe and 1 in the USA) to ensure global representation. Ethics and dissemination The study will be performed according to the Helsinki declaration. All results from the study, including inconclusive or negative results, will be published in peer-reviewed indexed journals. The study will involve different stakeholder groups to ensure that the developed COS will be suitable and well accepted.

Distinguishing hyperhidrosis and normal physiological sweat production: new data and review of hyperhidrosis data for 1980-2013.

Hyperhidrosis is a condition in which the production of sweat is abnormally increased. No objective criteria for the diagnosis of hyperhidrosis exist, mainly because reference intervals for normal physiological sweat production at rest are unknown.

Severe hidradenitis suppurativa responding to treatment with secukinumab: A case report

An inappropriate immunological response to an unknown antigen has been suggested to play a role in the pathogenesis of hidradenitis suppurativa (HS). Studies have identified elevated levels of several proinflammatory cytokines, including interleukin (IL)‐17A and tumour necrosis factor‐α, nominating these as possible therapeutic targets.1 Secukinumab is an IL‐17A monoclonal antibody, which binds to IL‐17A and inhibits the cytokine interaction with the IL‐17 receptors, inhibiting the inflammatory cascade. Here we report a case of a 47‐year‐old man, with Hurley stage III lesions on the neck, axillae, breasts, genital skin and buttocks, who had experienced only temporary benefit from different medical treatments over several years. After 12 weeks of treatment with secukinumab, the number of lesions reported by the patient within the period of the last 4 weeks was reduced from 23 to seven, his pain visual analogue scale (VAS) score was reduced from 5 to 3 and pain/utility/handicap VAS score was reduced from 7 to 4. These results may be taken to imply that IL‐17 blockade could provide a possible therapeutic approach in the treatment of HS.

A pilot study of unemployment in Hidradenitis Suppurativa Patients in Denmark

Hidradenitis Suppurativa (HS) is a chronic, inflammatory and relapsing skin disease, characterized by repeated outbreaks of painful inflamed nodules in the apocrine gland-bearing regions (armpits, genital area, groin, breasts and perianal region). These nodules can progress to abscesses, sinus tracts (tunnels) and scarring. (1) The estimated prevalence is 1-4% worldwide and HS is approximately three times more common in women than in men. (1) HS is associated with significant disability and handicap. The lesions are often painful and lead to loss of mobility. This article is protected by copyright. All rights reserved.

Investigational drugs in clinical trials for Hidradenitis Suppurativa

ABSTRACT Introduction: Hidradenitis suppurativa is a chronic skin disease with a significant unmet need for treatment options. Randomized controlled trials are few and only a single drug (adalimumab) has Hidradenitis as a registered indication. Areas covered: The clinicaltrials.gov and the EudraCT clinical trials register for reported trials on Hidradenitis Suppurativa was searched on the 22–06-2017. Trials for upcoming new drugs for HS are reported focusing on drugs in phase I and II trials. Expert opinion: Currently, MABp1, Secukinumab, CJM112, Apremilast and IFX-1 are being investigated in Phase I and II trials and offer theoretical and promising new treatment options. A trial with the drug MEDI8968 has been terminated with disappointing results. Metformin, Botulinum Toxin B, Provodine, Benzoyl Peroxide and intralesional triamcinolone are being tested as well. Treatment of Hidradenitis remains a challenge and quality RTCs are needed. Studies indicates a range of potential targets for therapy such as interleukin-1 and interleukin-17, but ‘broad-spectrum’ immunosuppressants like phosphodiesterase-4 inhibitors are being examined as well. A range of outcomes, including Physician Global Assessment, Sartorius scores and hidradenitis suppurativa clinical response are used in these trials, making future meta-analysis of the data difficult.

Towards global consensus on core outcomes for Hidradenitis Suppurativa research: An update from the HISTORIC consensus meetings I and II

A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed‐upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e‐Delphi surveys. In this manuscript, we describe two in‐person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items.

A core domain set for hidradenitis suppurativa trial outcomes: an international Delphi process

There is no consensus on core outcome domains for hidradenitis suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials likely leads to outcome‐reporting bias and limits the ability to synthesize evidence.

Hidradenitis suppurativa treated with secukinumab

Hidradenitis suppurativa (HS) is a serious skin disease. The cause of HS not known, but it is thought that a disturbance in the immune systems response plays an important role. Studies have found elevated levels of small proteins called cytokines in HS skin. Cytokines are signalling molecules that cells of the immune system use to communicate with each other. Some cytokines cause more inflammation in the skin and others reduce it. IL‐17A is one of the cytokines that cause inflammation, and it was found to be elevated in HS skin. If you remove IL‐17A from the skin tissue, inflammation is reduced and may even disappear. Secukinumab is an antibody that binds and destroys IL‐17A. Because there is a lot of IL‐17A in the skin of HS patients, we have tried this new treatment in a patient with severe disease. Our patient is a 47‐year‐old man, with severe HS. He has been treated for many years and only had temporary benefit from several other treatments that have been tried. We carefully recorded the patients experience of the treatment, comparing the results at the start of treatment with those after 12 weeks of treatment. After treatment with secukinumab the patient reported fewer boils (going from 23 to 7); less pain (going from 5 to 3 on a ten point scale) and less pain/utility loss/handicap (going from 7 to 4 on a ten point scale). The results may be taken to imply that medications targeting IL‐17A could provide a possible treatment approach for HS in the future.

Core domain set for hidradenitis suppurativa trial outcomes

Hidradenitis suppurativa (HS) is a skin condition that causes painful swollen red bumps in the folds of the body (underarms, under breasts, groin, and buttocks). It can be mistaken for bacterial abscess or boils, but HS is not caused by bacteria. HS occurs in about 0.1% to 4% of people worldwide. This study aimed to find out what clinical trials for HS should measure, such as symptoms (e.g. pain, itch), physical changes (e.g. skin redness or swelling), or impact on peoples lives (e.g. quality of life). To do this, the study included two groups: people with HS and healthcare providers (physicians, pharmaceutical industry representatives, and regulatory representatives) and conducted online surveys and in‐person meetings with presentations and discussions as well as surveys to gather opinions on which measures to include. Thirteen countries and four continents were represented. The result of the meetings, discussions, and surveys showed that at least 70% of the people with HS and healthcare providers recommended that clinical trials include measures of: (1) pain (2) physical changes due to HS (e.g. redness); (3) quality of life changes due to HS specifically; (4) changes in the course of HS (e.g. flare‐ups) (5) global rating (i.e. overall rating, considering everything, of the severity of the condition) and (6) other symptoms (fatigue and drainage). This work is important because it included many different types of people who contribute to HS treatment, including the people who have HS, develop or regulate treatments, and treat people with HS. More work is coming and it will focus on how to measure in trials treating HS (what instruments to use).

Idiopathic localised unilateral hyperhidrosis in a 7-year-old girl: a case report.

Sweating is a physiological process, which is vital for maintaining a constant body temperature and good grip function. Excessive sweating (hyperhidrosis) can on the contrary lead to severe social problems for the affected individual with a decreased quality of life (1). Primary or essential hyperhidrosis is seen symmetrically located to palms, feet, axillae and groins/anogential or generalised in larger areas such as head and trunk. Emotional as well as heat and effort trigger hyperhidrosis in genetic predisposed individuals (2). Essential hyperhidrosis must be differentiated from secondary hyperhidrosis, which is caused by disorders such as infection, malignancy, medication, neurological, or endocrine diseases (2). While axillary hyperhidrosis is quite common with a prevalence of about 1.4 % (3), hyperhidrosis on the body unilaterally or lesionally is very rare. It has been termed localised unilateral hyperhidrosis (LUH) (4) and has been associated with organic disorders such as malignancies (5) or neurological disorders (6), but it has also been reported after a trauma (4) or as idiopathic (7).